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Apoptotic cell death of cerebellar granule cells in rolling mouse Nagoya
Young Suk Suh1, Sen ich Oda, Yoon Hee Kang
1Department of Anatomy, College of Medicine and Human Genetics, Institute of Medicine Science Research Center, Korea University, 126-1 Anam-Dong 5-Ga, Sungbuk-Ku, Seoul 136-705, South Korea.
Abstract:
Rolling mouse Nagoya is a voltage dependent calcium channel alpha1A subunit mutant showing moderate ataxia. Granule cell loss was previously reported in the cerebellar vermis of homozygous rolling. Apoptotic cerebellar granule cell death was reported in homozygous leaner mice, an allele of rolling. Cerebella of 21-day-old rolling and wild type mice were used for terminal dUTP nick-end-labeling (TUNEL) assay and electron microscopic observation to understand the mechanism of granule cell loss in rolling mice. The number of TUNEL-positive cells was significantly increased in rolling. More TUNEL-positive cells were observed in the anterior cerebellar vermis compared with posterior. Condensation and fragmentation of granule cell nuclei in rolling mouse were observed frequently. These results suggest that apoptosis is one of the mechanisms of granule cell loss in the rolling cerebellum.
Insights
The rolling mouse Nagoya mutant exhibits significant cerebellar granule cell loss due to apoptosis. This programmed cell death, particularly in the anterior vermis, contributes to the observed ataxia in these mice.
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- Rolling mouse Nagoya is a mutant with a voltage-dependent calcium channel alpha1A subunit defect, exhibiting moderate ataxia.
- Previous studies reported granule cell loss in the cerebellar vermis of homozygous rolling mice and apoptotic cell death in leaner mice, an allele of rolling.
Purpose of the Study:
- To investigate the mechanism of cerebellar granule cell loss in rolling mice.
- To determine if apoptosis contributes to granule cell loss in the cerebellum of rolling mice.
Main Methods:
- Terminal dUTP nick-end-labeling (TUNEL) assay on cerebella from 21-day-old rolling and wild type mice.
- Electron microscopic observation of cerebellar tissues.
- Quantification and comparison of TUNEL-positive cells between rolling and wild type mice, and between anterior and posterior cerebellar vermis.
Main Results:
- A significant increase in TUNEL-positive cells was observed in the cerebella of rolling mice compared to wild type.
- Apoptotic cells, characterized by nuclear condensation and fragmentation, were frequently observed in rolling mouse cerebella.
- A higher density of TUNEL-positive cells was noted in the anterior cerebellar vermis of rolling mice compared to the posterior.
Conclusions:
- Apoptosis is a significant mechanism contributing to cerebellar granule cell loss in the rolling mouse model.
- The findings suggest a potential link between calcium channel dysfunction, apoptosis, and ataxia in the rolling mouse.
- Targeting apoptotic pathways may offer therapeutic strategies for cerebellar degeneration associated with calcium channelopathies.